Virtual crossmatch approach to maximize matching in paired kidney donation.

We developed and tested a new computer program to match maximal sets of incompatible live donor/recipient pairs from a national paired kidney donation (PKD) registry. Data of 32 incompatible pairs included ABO and 4 digit-high-resolution donor and recipient HLA antigens and recipient's HLA antibodies. Three test runs were compared, in which donors were excluded from matching to recipients with either donor-specific antibodies (DSA) >8000MFI (mean fluorescent intensity) at low-resolution (Run 1) or >8000MFI at high-resolution (Run 2) or >2000MFI and high-resolution (Run 3). Run 1 identified 22 703 possible combinations, with 20 pairs in the top ranked, Run 2 identified 24 113 combinations, with 19 pairs in the top ranked and Run 3 identified 8843 combinations, with 17 pairs in the top ranked. Review of DSA in Run 1 revealed that six recipients had DSA 2000-8000MFI causing a possible positive crossmatch resulting in breakdown of two 3-way and three 2-way chains. In Run 2, four recipients had DSA 2000-8000MFI, also potentially causing breakdown of three 2-way chains. The more prudent approach of excluding from matching recipients with DSA with >2000MFI reduces the probability of matched pairs having a positive crossmatch without significantly decreasing the number of possible transplants.

Thresholds of mangrove survival under rapid sea level rise.

The response of mangroves to high rates of relative sea level rise (RSLR) is poorly understood. We explore the limits of mangrove vertical accretion to sustained periods of RSLR in the final stages of deglaciation. The timing of initiation and rate of mangrove vertical accretion were compared with independently modeled rates of RSLR for 78 locations. Mangrove forests expanded between 9800 and 7500 years ago, vertically accreting thick sequences of organic sediments at a rate principally driven by the rate of RSLR, representing an important carbon sink. We found it very likely (>90% probability) that mangroves were unable to initiate sustained accretion when RSLR rates exceeded 6.1 millimeters per year. This threshold is likely to be surpassed on tropical coastlines within 30 years under high-emissions scenarios.

Mangrove Sedimentation and Response to Relative Sea-Level Rise.

Mangroves occur on upper intertidal shorelines in the tropics and subtropics. Complex hydrodynamic and salinity conditions, related primarily to elevation and hydroperiod, influence mangrove distributions; this review considers how these distributions change over time. Accumulation rates of allochthonous and autochthonous sediment, both inorganic and organic, vary between and within different settings. Abundant terrigenous sediment can form dynamic mudbanks, and tides redistribute sediment, contrasting with mangrove peat in sediment-starved carbonate settings. Sediments underlying mangroves sequester carbon but also contain paleoenvironmental records of adjustments to past sea-level changes. Radiometric dating indicates long-term sedimentation, whereas measurements made using surface elevation tables and marker horizons provide shorter perspectives, indicating shallow subsurface processes of root growth and substrate autocompaction. Many tropical deltas also experience deep subsidence, which augments relative sea-level rise. The persistence of mangroves implies an ability to cope with moderately high rates of relative sea-level rise. However, many human pressures threaten mangroves, resulting in a continuing decline in their extent throughout the tropics.

ChlVPP/PABlOE and radiotherapy in advanced Hodgkin's disease. The Central Lymphoma Group.

PURPOSE: The United Kingdom Central Lymphoma Group (CLG) has modified mechlorethamine, vincristine, procarbazine, and prednisone/doxorubicin, bleomycin, vinblastine, and dacarbazine (MOPP/ABVD) by substituting mechlorethamine with chlorambucil and dacarbazine with etoposide in the treatment of patients with advanced Hodgkin's disease (HD). Prednisolone is included in the bleomycin-containing combination, and the vinca alkaloids have been switched to balance the myelotoxicity of the two component regimens. PATIENTS AND METHODS: The resulting ChlVPP/PABlOE regimen is as follows: on days 1 to 14, chlorambucil 6 mg/m2 orally, procarbazine 100 mg/m2 orally, and prednisolone 30 mg/m2 orally; on days 1 and 8, vinblastine 6 mg/m2 intravenously (i.v.); on day 29, doxorubicin 40 mg/m2 i.v.; on days 29 and 36, vincristine 1.4 mg/m2 (maximum, 2 mg) i.v., and bleomycin 10 mg/m2 i.v.; on days 30, 31, and 32, etoposide 200 mg/m2/d orally; on days 29 to 43, inclusive, prednisolone, 30 mg/m2 orally. The second full cycle restarts on day 50. Treatment continues to maximum response plus two full cycles, but with a minimum of three full cycles. Radiotherapy is administered, after chemotherapy, to sites of previously bulky disease. Since 1983, 216 patients with previously untreated, advanced Hodgkin's disease (HD) have entered this study. RESULTS: The complete remission (CR) rate after chemotherapy was 73% (95% confidence interval [CI], 67% to 79%), and after additional radiotherapy was 85% (95% CI, 80% to 90%). The failure-free survival (FFS) rate at 5 years was 68% (95% CI, 61% to 74%), and the overall actuarial survival at 5 years was 78% (95% CI, 72% to 84%). The CR rate in patients in the poorer prognostic categories was high: 81% in patients with albumin levels less than 37 g/L, 79% in patients older than 40 years of age, 84% in stages IIIB plus i.v. disease, and 79% in patients presenting with B symptoms. As expected, nausea and vomiting were not major problems, although infection, often in the context of myelosuppression, complicated almost half the cases, and 29% of patients required admission at some stage for treatment of infection. CONCLUSION: In this multicenter study, ChlVPP/PABlOE produced results comparable to those reported for MOPP/ABVD, but with less nausea and vomiting. Treatment duration was shorter than in the original MOPP/ABVD regimen, and than that used in the Cancer and Leukemia Group B (CALGB) trial. It will now be compared with PABlOE alone.

Mitomycin, ifosfamide, and cisplatin in unresectable non-small-cell lung cancer: effects on survival and quality of life.

PURPOSE: Chemotherapy for non-small-cell lung cancer (NSCLC) remains controversial. We describe the two largest reported, randomized, parallel trials designed to determine whether the addition of chemotherapy influences duration and quality of life in localized, unresectable (mitomycin, ifosfamide, cisplatin [MIC]1 trial) and extensive (MIC2 trial) disease. PATIENTS AND METHODS: Ambulatory patients with NSCLC, aged 75 years or younger, with localized disease, were randomized in MIC1 to receive up to four cycles of chemotherapy (CT: mitomycin 6 mg/m(2), ifosfamide 3 g/m(2), and cisplatin 50 mg/m(2)) every 21 days, followed by radical radiotherapy (CT + RT) or radiotherapy (RT) alone. Extensive-stage patients were randomized in MIC2 to identical chemotherapy plus palliative care (CT + PC) or palliative care (PC) alone. Short-term change in quality of life (QOL) was assessed in a subgroup of patients. Data from the two trials were combined to allow multivariate and stratified survival analyses. RESULTS: Seven hundred ninety-seven eligible patients were randomized, 446 in MIC1 and 351 in MIC2. MIC CT improved survival in both trials (significantly in MIC2). The median survival time in MIC1 was 11.7 months (CT + RT) versus 9.7 months (RT alone) (P =.14); whereas in MIC2, median survival time was 6.7 months (CT + PC) compared with 4. 8 months (PC alone) (P =.03). QOL, assessed in 134 patients from start of trial to week 6, showed improvement with chemotherapy and deterioration with standard treatment. In the combined analysis of 797 randomized patients, the positive effect of MIC on survival was significant overall (P =.01) and after adjusting for prognostic factors (P =.01). CONCLUSION: MIC chemotherapy prolongs survival in unresectable NSCLC without compromising QOL.

Quality of life after treatment for testicular cancer--the patient's view.

Twenty-eight patients cured of testicular cancer by cisplatin-based chemotherapy were asked for their own views of the long-term psychological and social effects of their treatment. Their views were compared with a group of 34 testicular cancer patients cured by radiotherapy who were matched for age, social class and time since treatment. A category rating type questionnaire was used with questions concerning general health, subjective side-effects of treatment, employment, relationships, reproduction and mood. The principal differences were (1) the chemotherapy group reported a greater prevalence of physical side-effects, (2) the radiotherapy group reported greater anxiety and depression since treatment and (3) a significant number of patients in the chemotherapy group felt that their illness had had beneficial effects on their relationships with family and friends.

Ifosfamide, mitomycin and radiotherapy in non-small-cell lung cancer.

Ifosfamide and mitomycin C are two of the more active single agents in non-small-cell lung cancer (NSCLC). This study evaluates these drugs in combination followed by radiotherapy. A total of 33 ambulatory patients with inoperable NSCLC were treated with 5 g/m2 ifosfamide as a 24-h infusion, with the concurrent administration of sodium 2-mercaptoethane sulphonate (mesna; 160% of the ifosfamide dose) and 6 mg/m2 mitomycin C given as an i.v. bolus injection on the 2nd day. The median age of the patients was 61 years. In all, 20 patients had limited disease and 13, extensive disease. A total of 30 were assessable for response to chemotherapy, 8 of whom achieved a partial response (PR) and 5, a complete response (CR) (2 were verified bronchoscopically). The overall response rate was thus 43%. All but one response (a PR) were in patients with limited disease (LD). A total of 21 patients, including 13 responders, received thoracic irradiation (30 Gy in 8 fractions over 10 days) following chemotherapy. One PR was converted to a radiological CR. In all, 17 (55%) of the patients were alive at 1 year. All patients suffered chemotherapy-induced alopecia (WHO grade 3), but there were no treatment modifications due to myelosuppression, haemorrhagic cystitis or other toxicity. WHO grade 3 nausea and vomiting were seen in all patients. There was one treatment-related death. Combination therapy using ifosfamide and mitomycin C has useful activity in NSCLC.

A case of spontaneous regression of metastatic testicular teratoma.

We report the apparently spontaneous regression of metastatic disease in a young man who had previously undergone orchidectomy for a primary testicular teratoma. Serial serum tumour marker estimations revealed a sharp rise followed by a spontaneous decline in levels in a patient who had requested that chemotherapy be deferred for personal reasons.

Cooperation or conflict over child health surveillance? Views of key actors.

OBJECTIVE: To describe the views of general practitioners, health visitors, and clinical medical officers on child health surveillance, recent changes, perceptions of each other's roles, and attitudes to audit. DESIGN: Postal questionnaire survey. SETTING: Three health districts in North West Thames health region. SUBJECTS: All 602 general practitioners, 272 health visitors, and 42 clinical medical officers in these districts. MAIN MEASURES: Attitudes to and perceptions of child health surveillance and audit. Questionnaires were completed by 440 general practitioners (response rate 73%), 164 health visitors (60%), and 39 clinical medical officers (93%). RESULTS: Attitudes to child health surveillance were less positive among general practitioners than health visitors or clinical medical officers. Few respondents agreed that child health surveillance was a cost effective use of general practitioners' time (general practitioners 28%, 113/407; health visitors 28%, 40/145; clinical medical officers 39%, 15/39) and most thought that health visitors should carry out more of the doctors' examinations (68%, 262/387; 65%, 89/136; 66%, 25/38). General practitioners thought that clinical medical officers were less supportive than other relevant groups of their doing more child health surveillance. Most (72%, 105/146) health visitors thought that the 1990 contract had reduced parental choice of where to attend for child health surveillance. General practitioners were less enthusiastic than health visitors about most forms of clinical audit. CONCLUSIONS: Despite reservations about the impact of recent changes all groups were willing to explore innovative ways of delivering child health surveillance. IMPLICATIONS: There is scope for health visitors to increase their responsibilities and for more varied relationships between general practitioners and community child health doctors.

Paediatric home care in Tower Hamlets: a working partnership with parents.

OBJECTIVES: To describe the first two years of a paediatric home care service. DESIGN: Observational cross sectional study, 1989-91. SETTING: One inner London health district. PATIENTS: 611 children referred to the service; 50 children selected from those referred during the first year, whose parents were interviewed and whose general practitioners were invited to complete a questionnaire. MAIN MEASURES: Description and costs of service; views of parents and general practitioners of selected sample of children. RESULTS: In its second year the team received 303 referrals and made 4004 visits at a salary cost of 98000 pounds, an average of 323 pounds/referral and 24 pounds/visit. This represented a referral rate of 3.2% (258/7939) of inpatient episodes from the main referring hospital between 1 December 1989 and 30 November 1990. Of all referrals to the service, 343(56%) came from hospital inpatient wards. The service was used by disadvantaged and ethnic minority families. The children's parents (in 28(61%) families) and the home care team did a wide range of nursing tasks in the home. Parents of 47(94%) children sampled agreed to be interviewed, and those of 43(91%) found the service useful; guidance and support were most commonly appreciated (33, 70%). Parents of 25(53%) children said that hospital stay or attendance had been reduced or avoided. Parents and general practitioners disagreed on clinical responsibility in 10 children, and communication was a problem for some general practitioners. CONCLUSIONS: The service enabled children to receive advanced nursing care at home. Clinical responsibility should be agreed between parents and professionals at referral.

A special conditions register.

A special conditions register (SCR) linked to the child health system's register of all children has been in use in West Sussex since 1977. This paper describes the aims, organisation, and use of the SCR and gives examples of the aggregated data that may be obtained. Of the 155,000 children aged 0-17 resident in West Sussex in 1990, 4.3% were included on the SCR. Altogether 45.7% of children on the SCR had physical conditions with mild or no disability and 17.2% had moderate educational problems. The prevalence of severe hearing loss as defined was 1.7 per 1000 aged 5-17. The prevalence of diabetes mellitus was 1.2 per 1000 children aged 0-17. Validation of the SCR for diabetes mellitus found 35/36 of the eligible children were correctly registered and no child was incorrectly included. The conflicting priorities for maintaining a register for the care of individual children, for service planning, and for epidemiological research are discussed.

Paediatric home care in the UK.

Paediatric home care services in the UK were ascertained in 1991 and 1992. Respondents from 209 (97%) UK health districts and boards identified 62 general and 124 specialist paediatric home care services by January 1993, 15% having opened in the previous year. Of all UK children, 30% lived in a district with a general home care service. Five health regions had only specialist services. Districts differed widely in the availability of home care for different disorders. The home care services were small, general services employing a mean (SD) of 2.5 (1.6) whole time equivalent (WTE) nurses, and specialist services 1.3 (0.8) WTE nurses. Few services were available 24 hours a day. Funding arrangements were diverse and some services had difficulties in obtaining consumables and equipment for home use. Despite rapid growth there remains considerable scope for the development of paediatric home care throughout the UK.

What makes general practitioners do child health surveillance?

The contribution of different general practitioner characteristics, views, and experiences to the likelihood of their providing child health surveillance (CHS) was determined and their perceived training needs discovered. Family health service authority administrative data on the study population was combined with a postal questionnaire survey. Subjects were all general practitioners in three district health authorities in the North West Thames region. There were striking differences between districts in the proportion of practitioners undertaking CHS. General practitioners with paediatric training were three times more likely to do CHS. Women doctors were twice as likely to do CHS as men. The personal views of general practitioners were significantly associated with whether or not they undertook CHS. The CHS fee did not appear to be the major motivating factor. There was considerable demand for further training. The proportion of general practitioners undertaking CHS is likely to increase with the proportion of women and vocationally trained doctors. More local training is wanted, both by general practitioners already doing CHS and by those who would like to do it. Health authorities need to ensure that such training is convenient and continuing.

Women's health: potential for better coordination of services.

OBJECTIVE: To determine the proportion of women attending a genitourinary medicine clinic (GUMC) who are in need of contraception and the proportion of women attending a family planning clinic (FPC) who may require screening or treatment for sexually transmitted disease (STD). DESIGN: Cross-sectional survey. SETTING: A large FPC (17,600 attendances by women a year) and a large GUMC (20,060 attendances by women a year) in an inner London health district. SUBJECTS: All clients attending the two clinics in consecutive weeks (356 GUMC and 335 FPC). In addition a non-random cluster of other women attending the same clinics later in the year were interviewed in depth (21 GUMC and 20 FPC). RESULTS: Of women at the GUMC 10.4% (95% CI 7.2-13.6) were at risk of unwanted pregnancy and not using contraception. Women aged under 20 years and women not registered with a general practitioner (GP) were more likely to be in this group. A further 13.8% may have been using contraception unreliably as they were not obtaining contraception from a GP or FPC. Of women at the FPC 1.8% (95% CI 0.3-3.2) complained of symptoms of genitourinary infection. In-depth interviews showed that some women assumed the staff at both clinics would counsel them in all aspects of sexual health. CONCLUSIONS: The opportunities presented at GUMCs to reduce the incidence of unwanted pregnancy and the opportunities presented at FPCs to reduce the incidence and prevalence of STD should not be missed.

PIP: This study sought to determine the proportion of women attending a genitourinary medicine clinic (GUMC) who are in need of contraception and the proportion of women attending family planning clinics (FPC) who may require screening or treatment for sexually transmitted diseases (STDs). This cross-sectional survey conducted in an inner London health district focused on a large FPC (17,600 attendances by women/year) and a large GUMC (20,000 attendances by women/year). All clients investigated attended the 2 clinics in consecutive weeks (356 GUMC and 335 FPC). In addition, a nonrandom cluster of other women attending the same clinics later in the year were interviewed in depth (21 GUMC and 20 FPC). Of the women at the GUMC, 10.4% (95% CI 7.2-13.6) were at risk of unwanted pregnancy and were not using contraception. Women under age 20 and those not registered with a general practitioner (GP) were more likely to be in this group. A further 13.8% may have been using contraception unreliably since they had not obtained it from a GP or from the FPC. Of women at the FPC, 1.8% (95% CI 0.3-3.2) complained of symptoms of genitourinary infection. In-depth interviews showed that some women assumed the staff at both clinics would counsel them in all aspects of sexual health. The opportunities presented at GUMCs to reduce the incidence of unwanted pregnancy and the opportunities presented at FPCs to reduce the incidence and prevalence of STDs should not be missed.

Mitomycin, ifosfamide and cis-platin in non-small cell lung cancer: treatment good enough to compare.

Mitomycin, ifosfamide and cis-platin are three of the most active single agents in the chemotherapy of non-small cell lung cancer. We have combined them for a phase 2 study in patients with inoperable non-small cell lung cancer. The regimen ('MIC') comprised: mitomycin 6 mg m-2, ifosfamide 3 g m-2 and cis-platin 50 mg m-2, with routine use of lorazepam, dexamethasone and high dose metoclopramide for anti-emesis. Seventy-four ambulatory patients with untreated, limited (LD) or extensive (ED) disease have entered this study, and 66 are evaluable for response. Thirty patients (45%) have achieved partial remission and 7 (11%) complete remission, as assessed radiologically. The overall response rate is thus 56% (95% confidence interval 44%-68%). There have been 29/43 responses in LD (67%, 95% CI 53%-81%) and 8/23 in ED (35%, 95% CI 15%-55%). The median response duration, measured from the start of treatment is 8.75 months. The median survival for the whole group is 9.2 months. The principal toxicity was nausea and vomiting which was severe or prolonged (greater than 48 h) for one or more courses, in 9% of patients. Performance status (PS) and weight were assessed before, and 3 weeks after the last course of chemotherapy. Fifteen (of 31 evaluable) responders improved their PS and only 1 responder deteriorated. Twenty-one of the 28 evaluable non-responders had no change in PS. The difference in PS change between responders and non-responders is highly significant (P = 0.002). Thirty evaluable responders experienced a mean increase in weight of 2.9% with treatment, whereas 24 evaluable non-responders had a mean weight loss of 3.8%. This change is also highly significant (P = 0.0013). MIC is clearly a well tolerated regime and among the most active combinations in non-small cell lung cancer. It will now be tested in a randomized trial against no chemotherapy.

Testing new drugs in untreated small cell lung cancer may prejudice the results of standard treatment: a phase II study of oral idarubicin in extensive disease.

We have evaluated the orally active anthracycline idarubicin at a dose of 40 mg/m2 in divided doses over 24 hours in 21 previously untreated patients with extensive-stage small cell carcinoma of the lung (SCCL). Subsequent iv therapy was cyclophosphamide (1000 mg/m2), vincristine (1 mg/m2), and etoposide (120 mg/m2 iv on Day 1 and 250 mg/m2 orally in divided doses on Day 2; CVE) in patients who failed to respond to idarubicin and in relapsed patients. Three (14%) of 21 patients treated with idarubicin responded, with two complete responses (CR). Patients failing to respond promptly and those who relapsed were treated with CVE. Seven patients did not receive CVE for the following reasons: early death, four patients; early CNS disease, two; and refusal, one. Fourteen patients received CVE. Of 12 patients failing to respond to idarubicin, eight progressed on CVE, three achieved partial response (PR), and one achieved CR. Two idarubicin responders who received CVE achieved PR and CR. The median survival of all 21 patients was 6 months. For those with World Health Organization performance scores of 0 or 1 the median survival was 6.2 months and for the rest it was 2.6 months. Although CVE chemotherapy was instituted promptly in patients not responding to idarubicin, these results seem inferior to those previously seen in our center with standard treatment from the start. We believe that patients with extensive SCCL often require a rapid and more guaranteed response to their first treatment.

Chemotherapy for poor risk germ cell tumours. An independent evaluation of the POMB/ACE regime.

We have evaluated the 7-drug, alternating, high-dose cisplatin regime for germ cell tumours, designated POMB/ACE, in 55 patients with advanced malignant teratomas and 5 patients with bulky metastatic seminomas. All of the latter and 5 of the teratoma patients had relapsed following radiotherapy, chemotherapy or both. The previously untreated teratoma patients included 13 whose tumours were extragonadal. The primary testicular tumour patients comprised 16 with large and 21 with very large volume metastases according to the Medical Research Council criteria. POMB/ACE is effective therapy for poor risk patients with germ cell tumours (including those with the most advanced disease, i.e. hepatic and cerebral metastases) and prolonged treatment after marker normality seems unnecessary. It is a complex regime with significant toxicity and cannot be recommended for the treatment of patients with germ cell tumours who have an excellent prognosis with simpler, shorter and less toxic treatment.

Management preferences in stage I non-seminomatous germ cell tumours of the testis: an investigation among patients, controls and oncologists.

Increasingly, treatment choices leading to the same survival outcome can be offered to cancer patients (e.g. mastectomy or conservative surgery in early breast cancer). Two approaches available for post-orchidectomy, stage I patients with non-seminomatous germ cell tumours of the testis (NSGCTT), particularly those at high risk of relapse, include immediate adjuvant chemotherapy (two courses) or surveillance, with chemotherapy (typically four courses) given only on relapse. The aim of this study was to investigate which approach patients prefer. Questionnaires were given to newly diagnosed NSGCTT patients, to patients with previous experience of the two options and to non-cancer controls, including specialist testicular tumour oncologists. Participants were asked to choose between immediate chemotherapy, surveillance or for the doctor to decide, at recurrence risk levels ranging from 10% to 90%. Questionnaires were returned by 207 subjects in nine different groups. The risk thresholds at which subjects' management preference changed, within apparently homogeneous groups, varied greatly, although at least one subject in each group selected adjuvant chemotherapy at the lowest (10%) level of risk. Subjects tended to favour options of which they had previous experience. Cancer patients wanted the doctor to decide more frequently than controls. The wide variability observed makes it difficult to predict which option an individual will select. Personality factors and personal circumstances, other than specific experience and knowledge, are obviously influential. Many patients would prefer their doctor to decide, but variability among oncologists is as great as that among their patients.

Long-term toxicity of chemotherapy for testicular cancer--the cost of cure.

Twenty-seven patients cured of advanced testicular cancer by cisplatin-based chemotherapy have been assessed, a median of 30 months after start of treatment, for the long-term effects of such treatment on renal, endocrine, audiometric, reproductive and respiratory function. To control for the effects of orchidectomy on endocrine function a similar group of 11 patients cured by orchidectomy alone was also assessed. The extents of impairment in hearing and renal function were related to the total dose of cisplatin received, while the majority of patients had respiratory impairment which was, in part, related to the total dose of bleomycin. TSH was significantly higher in the chemotherapy group although serum free thyroxine and free T3 were normal in all. FSH was raised in 67% of the chemotherapy group although serum free thyroxine and free T3 were while LH was raised in 75% and 45% respectively. Serum testosterone was normal in all. The levels of FSH and LH were both independently correlated with age of the patient while FSH was higher in patients having more chemotherapy and had a tendency to fall towards normal with time since treatment. Over half the patients had normal sperm concentrations although 74% had a raised proportion of abnormal sperm. Indices of sperm function were worse in patients having more chemotherapy but sperm number increased towards normal with time since treatment, particularly after the second year. The long-term side-effects of chemotherapy for testicular cancer are thus generally mild but are largely irreversible and their severity is related to the total amount of chemotherapy received. As their longer term significance is not clear we would recommend that, in the treatment of testicular cancer, doses of chemotherapy are reduced to the minimum required for cure. Assessment of long-term side-effects of chemotherapy for testicular cancer should be a mandatory part of any study of such treatment and should be considered in any comparison of different therapies.

The role of metoclopramide in acute and delayed chemotherapy induced emesis: a randomised double blind trial.

High dose metoclopramide is an effective anti-emetic for use with cisplatin containing chemotherapy regimens but can cause extrapyramidal reactions. Lorazepam and dexamethasone are increasingly being used to alleviate chemotherapy induced emesis. This trial has assessed the contribution of high dose metoclopramide to anti-emetic control when given with dexamethasone and lorazepam. Eight-one patients receiving chemotherapy, mainly for gynaecological malignancy, entered a randomised double blind cross-over trial comparing dexamethasone and lorazepam with or without a 24 h metoclopramide infusion. This was followed by oral dexamethasone with or without oral metoclopramide for three further days depending on the initial randomisation. Sixty-one patients were fully evaluable. Fifty-five received cisplatin containing regimens and six non-cisplatin regimens. There was a significant reduction in the number of episodes of vomiting during the first 24 h in patients receiving the metoclopramide combination (P = 0.0001). On first exposure to chemotherapy 45% of patients receiving dexamethasone, lorazepam and high dose metoclopramide had no vomiting while 67% had two episodes or less ('major control'). This compared to 11% total control and 25% major control in those receiving dexamethasone, lorazepam and placebo. The control of nausea in the first 24 h was also improved (P = 0.0001). There was no difference in the degree of nausea or vomiting during the following three weeks between those receiving oral dexamethasone alone and those receiving dexamethasone and metoclopramide. Both groups showed a significant increase in nausea in the three weeks following the second course of treatment when compared to the first (P = 0.0007). Extrapyramidal reactions were recorded in 11.5% of patients receiving metoclopramide. More patients stated a preference for the metoclopramide combination although this was not statistically significant (chi 2(1) = 0.29, P = 0.59). In conclusion the combination of dexamethasone and lorazepam can give major control of emesis in 25% of patients receiving very emetogenic chemotherapy. The addition of metoclopramide increases this to 67% on first exposure to chemotherapy, but at the expense of extrapyramidal reactions in 11.5%.